Nomogram to Predict Risk of Postoperative Urinary Retention in Women Undergoing Pelvic Reconstructive Surgery.

OBJECTIVE: To develop a nomogram that determines an individual's risk of postoperative urinary retention (POUR) following pelvic floor reconstructive surgery. METHODS: We performed a retrospective chart review of women who underwent reconstructive surgery for pelvic organ prolapse and/or stress urinary incontinence. Short-term POUR was defined as failure of the trial of void (post-void residual >150 mL with a void of >200 mL) on postoperative day one or the need for re-catheterization in the first 2 postoperative days. Potential pre- and intraoperative risk factors for POUR were compared between patients with and without POUR. Multivariate binary logistic regression analysis with best-subsets variable selection was used to create a predictive nomogram. RESULTS: Most patients (275 of 332) had concomitant or combined procedures. The overall incidence of POUR was 31% (103 of 332 patients). The risk of POUR was higher for patients with high-grade anterior prolapse and those who had undergone anterior vaginal repair, vaginal hysterectomy, or a laparoscopic sling procedure. Patients who did not experience POUR tended to have fewer co-morbidities and were more likely to have undergone laparoscopic colposacropexy. Risk factors for POUR in the nomogram were diabetes, multiple medical co-morbidities, laparoscopic sling procedure, anterior vaginal repair, laparoscopic colposacropexy, and vaginal hysterectomy. The nomogram allows clinicians to calculate a patient's risk of POUR (range <10% to >80%). CONCLUSION: While the predictive nomogram in this study was developed using a single surgeon's case series and may not be generalizable to all surgeons, it demonstrates that the risk of POUR may be predicted based on clinical characteristics and the type of surgery performed. This kind of prediction model could help guide clinicians in preoperative patient counseling.

map3k1 suppresses terminal differentiation of migratory eye progenitors in planarian regeneration.

Proper stem cell targeting and differentiation is necessary for regeneration to succeed. In organisms capable of whole body regeneration, considerable progress has been made identifying wound signals initiating this process, but the mechanisms that control the differentiation of progenitors into mature organs are not fully understood. Using the planarian as a model system, we identify a novel function for map3k1, a MAP3K family member possessing both kinase and ubiquitin ligase domains, to negatively regulate terminal differentiation of stem cells during eye regeneration. Inhibition of map3k1 caused the formation of multiple ectopic eyes within the head, but without controlling overall head, brain, or body patterning. By contrast, other known regulators of planarian eye patterning like WntA and notum also regulate head regionalization, suggesting map3k1 acts distinctly. Eye resection and regeneration experiments suggest that unlike Wnt signaling perturbation, map3k1 inhibition did not shift the target destination of eye formation in the animal. Instead, map3k1(RNAi) ectopic eyes emerge in the regions normally occupied by migratory eye progenitors, and the onset of ectopic eyes after map3k1 inhibition coincides with a reduction to eye progenitor numbers. Furthermore, RNAi dosing experiments indicate that progenitors closer to their normal target are relatively more sensitive to the effects of map3k1, implicating this factors in controlling the site of terminal differentiation. Eye phenotypes were also observed after inhibition of map2k4, map2k7, jnk, and p38 , identifying a putative pathway through which map3k1 prevents differentiation. Together, these results suggest that map3k1 regulates a novel control point in the eye regeneration pathway which suppresses the terminal differentiation of progenitors during their migration to target destinations. Author Summary: During adult regeneration, progenitors must migrate and differentiate at the proper locations in order to successfully restore lost or damaged organs and tissues, yet the mechanisms underlying these abilities are not fully understood. The planarian eye is a model to study this problem, because this organ is regenerated using migratory progenitors that travel long distances through the body in an undifferentiated state prior to terminal differentiation upon their arrival at target destinations. We determined that a pathway involving the MAP kinase kinase kinase map3k1 holds planarian eye progenitors in an undifferentiated state during their transit. Inhibition of map3k1 caused a dramatic body transformation in which migratory progenitors differentiate inappropriately early, and in the wrong locations, into mature eyes. By analyzing this phenotype and measuring the change to eye progenitor abundance after map3k1 inhibition, we found that map3k1 prevents ectopic differentiation of eye cells rather than mediating body-wide patterning through the Wnt pathway. Our study argues that whole-body regeneration mechanisms involve separate steps to control patterning and progenitor differentiation.

Cost comparison of the laparoscopic burch colposuspension, laparoscopic two-team sling procedure, and the transobturator tape procedure for the treatment of stress urinary incontinence.

OBJECTIVE: To compare medical costs of three surgical procedures for the treatment of primary stress urinary incontinence: the laparoscopic Burch colposuspension procedure, the laparoscopic two-team sling procedure, and the transobturator tape (TOT) procedure. METHODS: We performed a retrospective observational study of isolated minimally invasive surgical procedures (no concomitant surgery) in 18 women with primary stress incontinence. Six women underwent a laparoscopic Burch colposuspension procedure, six underwent a laparoscopic two-team sling, and six underwent a TOT procedure. The main outcome measure was the mean aggregated medical cost per patient treated. Itemized calculations were made for (1) equipment costs; (2) surgeon, surgical assistant, and anaesthesiologist reimbursements; (3) nursing costs; (4) operating and recovery room costs; and (5) costs of stay in hospital. RESULTS: The mean cost per patient undergoing a TOT procedure was $2547 (95% CI $2260 to $2833); for a laparoscopic Burch colposuspension it was $4354 (95% CI $3465 to $5244); and for a laparoscopic two-team sling procedure it was $5393 (95% CI $4959 to $5826). Significant differences were found across procedures using a one-way ANOVA. A TOT was lower in cost than both a Burch procedure, with a mean cost difference of $1807.88 (P < 0.001), and a sling procedure, with a mean cost difference of $2834.73 (P < 0.001). CONCLUSION: A transobturator tape procedure has less direct medical costs than a laparoscopic Burch colposuspension or a laparoscopic two-team sling procedure in the surgical treatment of stress urinary incontinence.

Dual induction of TREM2 and tolerance-related transcript, Tmem176b, in amyloid transgenic mice: implications for vaccine-based therapies for Alzheimer's disease.

Vaccine-based autoimmune (anti-amyloid) treatments are currently being examined for their therapeutic potential in Alzheimer's disease. In the present study we examined, in a transgenic model of amyloid pathology, the expression of two molecules previously implicated in decreasing the severity of autoimmune responses: TREM2 (triggering receptor expressed on myeloid cells 2) and the intracellular tolerance-associated transcript, Tmem176b (transmembrane domain protein 176b). In situ hybridization analysis revealed that both molecules were highly expressed in plaque-associated microglia, but their expression defined two different zones of plaque-associated activation. Tmem176b expression was highest in the inner zone of amyloid plaques, whereas TREM2 expression was highest in the outer zone. Induced expression of TREM2 occurred co-incident with detection of thioflavine-S-positive amyloid deposits. Transfection studies revealed that expression of TREM2 correlated negatively with motility, but correlated positively with the ability of microglia to stimulate CD4(+) T-cell proliferation, TNF (tumour necrosis factor) and CCL2 (chemokine ligand 2) production, but not IFNgamma (interferon gamma) production. TREM2 expression also showed a positive correlation with amyloid phagocytosis in unactivated cells. However, activating cells with LPS (lipopolysaccharide), but not IFNgamma, reduced the correlation between TREM2 expression and phagocytosis. Transfection of Tmem176b into both microglial and macrophage cell lines increased apoptosis. Taken together, these data suggest that, in vivo, Tmem176b(+) cells in closest apposition to amyloid may be the least able to clear amyloid. Conversely, the phagocytic TREM2(+) microglia on the plaque outer zones are positioned to capture and present self-antigens to CNS (central nervous system)-infiltrating lymphocytes without promoting pro-inflammatory lymphocyte responses. Instead, plaque-associated TREM2(+) microglia have the potential to evoke neuroprotective immune responses that may serve to support CNS function during pro-inflammatory anti-amyloid immune therapies.